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TP53 mutations in CLL
3B). Combining the group of patients with TP53ab with VAF 1-100%, the association persisted when omitting del(17p) patients (P≤0.001) (Figure 3C). Four patients with minor TP53muts were still alive and in complete remis- sion at end of follow up (Figure 3B and C). There was no difference in survival between patients harboring one TP53mut with a VAF greater than 1% (VAF 1-100%) and patients with more than one TP53mut (P=0.85) (data not shown). Although both patients receiving first-line treat- ment (n=50) and patients receiving later lines of treatment (n=11) were included in the cohort at time of treatment, TP53 status demonstrated a similar negative impact on OS in both subcohorts (data not shown).
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TP53 status may predict outcome in newly diagnosed patients with unmutated IGHV status
As most patients with TP53ab at time of treatment were also IGHV unmutated (IGHV-U) (Online Supplementary Table S8), we explored the synergy between TP53ab and IGHV mutational status for newly diagnosed patients. For patients with mutated IGHV (IGHV-M), TP53ab [whether low burden or high burden, including 4 patients with del(17p)] did not impact OS or TFS. However, for patients with IGHV-U status, high burden TP53ab [including 3 patients with del(17p)] significantly impacted both OS and TFS (P=0.036 and P=0.005, respectively) (Figure 4).
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Figure 2. Overall (OS) and treatment-free survival (TFS) in newly diagnosed patients. Kaplan-Meier curves comparing OS (panels A, C, E) and TFS (panels B, D, F) based on (A and B) TP53 aberrations stratified based on variant allele frequencies (VAF) including del(17p) with 10% cut-off or (C and D) 1% and 10% cut- off. (E and F) Del(17p) and subgroups with TP53 muta- tions without del(17p) [(TP53mut w/o del(17p)] ana- lyzed separately. P-values are indicated in the tables within the panels.
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